Clinical pharmacokinetics and metabolism of nimesulide

Abstract

Nimesulide is a selective COX-2 inhibitor used in a variety of inflammatory, pain and fever states. After oral administration the drug is rapidly and extensively absorbed. Nimesulide is rapidly distributed, extensively bound to albumin and eliminated with a terminal half-life of about 4 h. Excretion of the unchanged drug in urine and faeces is negligible. Nimesulide is mainly cleared from the body by metabolic transformation and the principal active metabolite is the 4′-hydroxyl derivative (M1). After oral administration, nimesulide shows linear pharmacokinetics in the dose range from 25 to 100 mg. The usual therapeutic regimen is 100 mg p.o. twice daily. The pharmacokinetic profiles of nimesulide and M1 in children and elderly do not differ from those of healthy young subjects. The pharmacokinetics of nimesulide and M1 are not altered in moderate renal impairment. Pharmacokinetic interactions between nimesulide and other drugs given in combination were absent or of no clinical significance.

Lücker, P. W. (1993b). Report of the study on the pharmacokinetics of nimesulide and its main metabolite 4-OH-nimesulide after oral administration of three different doses in healthy male volunteers. Helsinn Healthcare, data on file. TSD No. 5781E.